Beamion LUNG-1：HER2異常を有する進行又は転移性固形癌患者を対象としたzongertinib（BI 1810631）単剤療法の非盲検第I相用量漸増，用量確認及び拡大試験

試験ID jRCT2031210165

最終情報更新日：2024年12月22日

基本情報

• 試験ID: jRCT2031210165
• 研究名称 / Scientific Title（Acronym）: Beamion LUNG-1：HER2異常を有する進行又は転移性固形癌患者を対象としたzongertinib（BI 1810631）単剤療法の非盲検第I相用量漸増，用量確認及び拡大試験
• 研究名称 / Scientific Title（Acronym）: Beamion LUNG-1: An open label, Phase I dose escalation trial, with dose confirmation and expansion, of zongertinib (BI1810631) as monotherapy in patients with advanced or metastatic solid tumors with HER2 aberrations
• 平易な研究名称 / Public Title（Acronym）: A study to test different doses of BI 1810631 in people with different types of advanced cancer (solid tumours with changes in the HER2 gene).
• 試験進捗状況/Recruitment status: 参加者募集中
• 試験進捗状況/Recruitment status: Recruiting
• 登録日時: 2021年6月28日
• 最終情報更新日: 2024年12月22日
• 他の臨床研究登録機関発行の研究番号: NCT04886804

試験概要

• 試験実施地域 / Region: 日本
• 試験実施地域 / Region: USA,Japan,Netherlands,Japan,China,Japan
• 実施都道府県: 東京都
• 目標症例数/Target sample size: 96
• 対象疾患 / Health condition(s) or Problem(s) studied: 非小細胞肺癌
• 対象疾患 / Health condition(s) or Problem(s) studied: NSCLC
• 試験のタイプ / Study type: 介入
• 試験のタイプ / Study type: Interventional

介入1

第Ia相用量漸増の開始用量は以下のとおりである。
・BIDスケジュール：15 mg 1日2回
・QDスケジュール：60 mg 1日1回（DECから他に提案がない限り）
各用量漸増ステップは，用量漸増委員会（DEC）が決定する。
第Ib相用量拡大パートの用量は，用量漸増パート実施中に決定する。

介入2

第Ia相用量漸増の開始用量は以下のとおりである。
・BIDスケジュール：15 mg 1日2回
・QDスケジュール：60 mg 1日1回（DECから他に提案がない限り）
各用量漸増ステップは，用量漸増委員会（DEC）が決定する。
第Ib相用量拡大パートの用量は，用量漸増パート実施中に決定する。

介入3

第Ia相用量漸増の開始用量は以下のとおりである。
・BIDスケジュール：15 mg 1日2回
・QDスケジュール：60 mg 1日1回（DECから他に提案がない限り）
各用量漸増ステップは，用量漸増委員会（DEC）が決定する。
第Ib相用量拡大パートの用量は，用量漸増パート実施中に決定する。

介入4

第Ia相用量漸増の開始用量は以下のとおりである。
・BIDスケジュール：15 mg 1日2回
・QDスケジュール：60 mg 1日1回（DECから他に提案がない限り）
各用量漸増ステップは，用量漸増委員会（DEC）が決定する。
第Ib相用量拡大パートの用量は，用量漸増パート実施中に決定する。

介入5

第Ia相用量漸増の開始用量は以下のとおりである。
・BIDスケジュール：15 mg 1日2回
・QDスケジュール：60 mg 1日1回（DECから他に提案がない限り）
各用量漸増ステップは，用量漸増委員会（DEC）が決定する。
第Ib相用量拡大パートの用量は，用量漸増パート実施中に決定する。

介入6

第Ia相用量漸増の開始用量は以下のとおりである。
・BIDスケジュール：15 mg 1日2回
・QDスケジュール：60 mg 1日1回（DECから他に提案がない限り）
各用量漸増ステップは，用量漸増委員会（DEC）が決定する。
第Ib相用量拡大パートの用量は，用量漸増パート実施中に決定する。

介入7

第Ia相用量漸増の開始用量は以下のとおりである。
・BIDスケジュール：15 mg 1日2回
・QDスケジュール：60 mg 1日1回（DECから他に提案がない限り）
各用量漸増ステップは，用量漸増委員会（DEC）が決定する。
第Ib相用量拡大パートの用量は，用量漸増パート実施中に決定する。

主要評価項目 / Primary outcomes

第Ia相パート
-MTD評価期間中の用量制限毒性（DLT）発現数に基づくMTD
-MTD評価期間中にDLTを発現した患者数
第Ib相パート
-固形がんの治療効果判定のためのガイドライン（RECIST）第1.1版に基づく客観的奏効（OR）

主要評価項目 / Primary outcomes

Phase Ia part of the trial:
-MTD, based on number of dose-limiting toxicities (DLTs) during the MTD evaluation period.
-Number of patients with DLTs in the MTD evaluation period.
Phase Ib part of the trial:
-Objective response (OR), according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1

副次評価項目 / Secondary outcomes

Phase Ia part of the trial:
-Number of patients experiencing DLTs during the entire treatment period.
-PK parameters of BI 1810631: Cmax and AUC0-t2
Phase Ib part of the trial:
-Duration of objective response (DoR)
-Disease control (DC)
-Duration of disease control (DoDC)
-Progression-free survival (PFS)
-Number of patients experiencing DLTs during the entire treatment period
-PK parameters of BI 1810631: Cmax and AUC0-t2

適格性

• 年齢（下限）/ Age minimum: 20歳以上
• 年齢（下限）/ Age minimum: >= 20age old
• 年齢（上限）/ Age maximum: Not applicable
• 性別 / Gender: 男女両方
• 性別 / Gender: Both

選択基準 / Include criteria

1.Histologically or cytologically confirmed diagnosis of an advanced, unresectable and or metastatic non haematologic malignancy. Patient must have measurable or evaluable lesions (according to Response Evaluation Criteria In Solid Tumors RECIST1.1).
2.Eastern Cooperative Oncology Group score of 0 or 1
3.Availability and patient willingness to provide a sample of tumour for confirmation of the patients Human epidermal growth factor receptor 2 (HER2) status. This sample can be archival material obtained at any time prior to study enrollment.
4.Patient willing to undergo a fresh tumour biopsy prior to first treatment and also 5 to 7 hours (h) after any treatment with BI 1810631 during cycle 1 (except biopsies of brain metastases) for pharmacodynamic assessments
5.Adequate organ function defined as all of the following: Absolute neutrophil count (ANC) greater than or equal to 1.5 times 109 perL (greater than or equal to1.5 times 103 per micro L) (greater than or equal to 1500 per mm3);haemoglobin greater than or equal to 9.0 g per dL (greater than or equal to 90 g per L) (greater than or equal to 5.6 mmol per L); platelets greater than or equal to 100 times 109 per L (100 times 103 per micro L) (100 times 103 per mm3) without the use of hematopoietic growth factors within 4 weeks of start of trial medication Total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN), except for patients with Gilbert's syndrome: total bilirubin less than or equal to 3 times ULN or direct bilirubin less than or equal to 1.5 times ULN Creatinine less than or equal to 1.5 times ULN. If creatinine is more than 1.5 times ULN, patient is eligible if concurrent creatinine clearance greater than or equal to 50 ml per min (measured or calculated by Chronic Kidney Disease Epidemiology (CKD EPI) formula or Japanese version of CKD EPI formula for Japanese patients) Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 3 times ULN if no demonstrable liver metastases, or otherwise less than or equal to 5 times ULN if transaminase elevation is attributable to liver metastases Alkaline Phosphatase less than 5 times ULN
6.Recovered from any previous therapy related toxicity to less than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at start of treatment (except for alopecia, stable sensory neuropathy and hypothyroidism (patients on thyroid replacement therapy) which must be less than or equal to CTCAE Grade 2)
7.Life expectancy of at least 12 weeks at the start of treatment in the opinion of the investigator
8.At least 18 years of age at the time of consent or over the legal age of consent in countries where that is greater than 18 years.
9.Signed and dated written informed consent in accordance with International Council on Harmonisation Good Clinical Practice (ICH GCP) and local legislation prior to admission to the trial Male or female patients.
10.Women of childbearing potential (WOCBP)1 and men who are able to father a child must be ready and able to use highly effective methods of birth control per International Council on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1 percent per year when used consistently and correctly
Additional Inclusion criteria for Phase Ia;
Patients with a documented diagnosis of HER2 aberration: overexpression OR gene amplification OR non synonymous somatic mutation OR gene rearrangement involving HER2 or Neuregulin 1 (NRG1) Patient who has failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Patient must have exhausted, or not be a suitable candidate for, available treatment options known to prolong survival for their disease
Additional Inclusion criteria for Phase Ib;
Patient with documented HER2 tyrosine kinase domain mutation positive non small cell lung cancer (NSCLC) as per central lab results Patient who had received, in the advanced or metastatic setting, at least one line of systemic therapy. Patients with NSCLC harboring additionally genomic aberrations for which approved targeted therapy is available such as but not limited to non resistant epidermal growth factor receptor (EGFR) mutations, EGFR T790M mutation, Anaplastic lymphoma kinase (ALK) rearrangement, reactive oxygen species (ROS) re arrangement, and v raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutation, must have received prior treatment with an approved targeted therapy.

除外基準 / Exclude criteria

1.Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to first trial treatment or planned within 6 months after screening
2.Previous or concomitant malignancies other than the one treated in this trial within the last 2 years, except; a)effectively treated non-melanoma skin cancers b)effectively treated carcinoma in situ of the cervix c)effectively treated ductal carcinoma in situ d)other effectively treated malignancy that is considered cured by local treatment.
3.Treatment with a systemic anti-cancer therapy or investigational drug within 21 days or 5 half-lives (whichever is shorter) of the first treatment with the study medication
4.Patients who must or wish to continue the intake of restricted medication or any drug considered likely to interfere with the safe conduct of the trial.
5.Use of concomitant medications that are narrow therapeutic index drugs that are substrates of P-Glycoprotein (P-gp) or Breast Cancer Resistance Protein (BCRP) (e.g. digoxin, dabigatran etexilate)
6.Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors
7.Treatment with strong Cytochrome P450 3A (CYP3A) inducers

責任研究者

• 責任研究者 / Name of lead principal investigator: Shintaro Ogawa
• 部署名 / Division: Boehringer Ingelheim
• 住所 / Address: 2-1-1, Osaki, Shinagawa-ku, Tokyo Tokyo Japan 141-6017
• 電話 / Telephone: [phone]
• 実施責任組織 / Affiliation: 小川 進太郎
• 実施責任組織 / Affiliation: Boehringer Ingelheim

試験問い合わせ窓口

• 住所 / Address: 2-1-1, Osaki, Shinagawa-ku, Tokyo Tokyo Japan 141-6017
• 電話 / Telephone: [phone]
• E-mail: [e-mail]
• 担当者 / Name of contact person: Tomohiro Yamagami